Be yourself, everyone else is already taken.

342 Pages·2014·7.13 MB·English

“Be yourself, everyone else is already taken.”
Oscar Wilde (1854-1900)

Ghent University
Faculty of Pharmaceutical Sciences

DEVELOPMENT AND VALIDATION OF PROCESS ANALYTICAL
METHODS FOR A CONTINUOUS PHARMACEUTICAL
MANUFACTURING PROCESS OF TABLETS BASED ON WET
GRANULATION

Margot FONTEYNE
Master in Drug Development

Thesis submitted to obtain the degree of Doctor in Pharmaceutical Sciences
2014

Promoter: Prof. Dr. T. De Beer
Laboratory of Pharmaceutical Process Analytical Technology
Co-promoter: Prof. Dr. J.P. Remon
Laboratory of Pharmaceutical Technology

The author, the promoter and the co-promoter give the authorization to consult and to copy
parts of this thesis for personal use only. Any other use is limited by the Laws of Copyright,
especially concerning the obligation to refer to the source whenever results are cited from
this thesis.

Ghent, July 3 2014

The author The promoter The co-promoter

Pharm. Margot Fonteyne Prof. Dr. Thomas De Beer Prof. Dr. Jean Paul Remon

This ship disembarked as early as 2008, setting sail to Copenhagen as its first destination. It
was Thomas De Beer who convinced me of the excellent learning possibilities up in the
north. Dr. Holger Grohganz and Prof. Jukka Rantanen determined the first sea route and
helped me navigating during this maiden voyage.
Once anchored back in Ghent, it was again Prof. Thomas De Beer who invited me to
continue the journey. I am very grateful for this chance, his most valued help during my
travel and the endless amount of great opportunities offered. Furthermore, I thank Prof.
Jean Paul Remon and Prof. Chris Vervaet for their technical support throughout the years.
During the past four years, seven young scientists stepped aboard. They all had their own
talents and their contribution to this work is highly appreciated. Carmen (Madrid),
Delphine (Ghent), Sandra (Porto), Niko (Kuopio), Henrika (Turku), Sofie (Ghent) and Ana
(Porto): Gracias, Dank je, Obrigado, Kiitos, Tack for your enthusiasm!
Furthermore, several great researchers hopped on and off the ship for a discussion or
collaboration: Prof. Damián Córdoba Díaz (Madrid), Prof. Niklas Sandler (Turku), Prof.
Vincent Bulone (Stockholm), Prof. Jarkko Ketolainen (Kuopio), Prof. Krist Gernaey
(Copenhagen), Prof. Ingmar Nopens (Ghent), Séverine Mortier (Ghent), Dr. Clare Strachan
(Helsinki), Maunu Toiviainen (Kuopio), Andrew Fussell (Twente), Sara Fraser (Dunedin),
Björn Peters (Kuopio), Søren Vinter Søgaard (Copenhagen), Julen Arruabarrena Gamboa
(Barcelona), Jacques De Beer (Brussels), Mario Hellings, Tom Van den Kerkhof (Beerse),
Rut Besseling, Ad Gerich, Wim Oostra (Oss), Fernanda Onofre (Brussels), Ilija Ilić
(Ljubljana), Qi Zhou (Stockholm) and Kaisa Naelapää (Copenhagen). Thank you!
Two very important crew members may not be forgotten: Jurgen and Liesbeth, thank you
for the countless discussions, practical help, reading of papers and much, much more!
Kris, Tomas, Dirk, Tessa and Alain, thanks for the support from the dockyard!
In 2011, this vessel navigated to the southern hemisphere to continue the research work.
Prof. Thomas Rades, thank you for accepting me in your group for these six months. I am
grateful to the FWO for financial support. Furthermore, a big thanks to all people who
helped me in Dunedin, both research- and otherwise: my office mates, the School of
Pharmacy staff and York Zoo’ers.
During long travels away from home, nothing is as important as a good atmosphere aboard.
Two shipmates were there from the start. Anneleen, you have set an example for us, it was
an honour to follow your wake. Lien, thank you for your friendship and endless support. To
my fellow PAT’ers: our galley-time was always great, and yes we dó laugh till our midriffs
hurt! Wim and Valerie, thanks for the many fun hours we’ve spend at both the North and
the South side! Everybody on the third deck has been very helpful, this has been highly
appreciated.
Luckily, during its journey, this boat could beach on several isles. I could say ‘isles of rest’,
but for sure they were not . Bloso-chaps and -gals, Vormers, thanks for clearing my head
every once in a while. This was as important as the real journey!
Of course, when sailing back into the harbour, it is great to have people waiting on the
quayside. To my parents, grandmothers, brothers, nieces, parents-in-law, family and friends:
thank you for the trust and support!
Benji, Kilo Alfa Uniform.
Margot, Basel 2014